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Cullinan Therapeutics (CGEM) presented updated data from Module C of the pivotal Phase 2b REZILIENT1 trial for zipalertinib at ESMO 2024. The study focused on patients with NSCLC harboring EGFR exon 20 insertion mutations who progressed after amivantamab treatment. Key findings include:
– 40% objective response rate (ORR) in 30 evaluable patients
– 90% disease control rate (DCR)
– 9.7 months median progression-free survival (PFS)
– Manageable safety profile with mostly grade 1/2 adverse events
The pivotal Phase 2b trial completed enrollment ahead of schedule. Cullinan’s partnership with Taiho involves a $275M upfront payment and potential for $130M in additional regulatory milestones, with a 50/50 profit share in the U.S.
Cullinan Therapeutics (CGEM) ha presentato dati aggiornati dal Modulo C del fondamentale studio di fase 2b REZILIENT1 per zipalertinib all’ESMO 2024. Lo studio si è concentrato su pazienti con NSCLC portatori di mutazioni di inserzione nell’esone 20 dell’EGFR che hanno mostrato progressione dopo il trattamento con amivantamab. I risultati principali includono:
– 40% di tasso di risposta obiettiva (ORR) in 30 pazienti valutabili
– 90% di tasso di controllo della malattia (DCR)
– 9,7 mesi di sopravvivenza libera da progressione mediana (PFS)
– Profilo di sicurezza gestibile con per lo più eventi avversi di grado 1/2
Lo studio di fase 2b cruciale ha completato l’arruolamento in anticipo rispetto al programma. La partnership di Cullinan con Taiho prevede un pagamento iniziale di 275 milioni di dollari e la possibilità di ulteriori 130 milioni di dollari in traguardi normativi, con una divisione dei profitti 50/50 negli Stati Uniti.
Cullinan Therapeutics (CGEM) presentó datos actualizados del Módulo C del ensayo pivotal de fase 2b REZILIENT1 para zipalertinib en ESMO 2024. El estudio se centró en pacientes con NSCLC portadores de mutaciones de inserción en el exón 20 de EGFR que progresaron tras el tratamiento con amivantamab. Los hallazgos clave incluyen:
– 40% de tasa de respuesta objetiva (ORR) en 30 pacientes evaluables
– 90% de tasa de control de la enfermedad (DCR)
– 9,7 meses de supervivencia libre de progresión mediana (PFS)
– Perfil de seguridad manejable con en su mayoría eventos adversos de grado 1/2
El ensayo pivotal de fase 2b completó la inclusión de pacientes antes de lo previsto. La asociación de Cullinan con Taiho incluye un pago inicial de 275 millones de dólares y un potencial de 130 millones de dólares en hitos regulatorios adicionales, con un reparto de beneficios 50/50 en EE. UU.
Cullinan Therapeutics (CGEM)는 ESMO 2024에서 zipalertinib에 대한 중대한 2b상 REZILIENT1 시험의 C 모듈에서 업데이트된 데이터를 발표했습니다. 이 연구는 EGFR 엑손 20 삽입 변이를 가진 NSCLC 환자 중 아미반타맙 치료 후 병이 진행된 환자들에 초점을 맞췄습니다. 주요 결과는 다음과 같습니다:
– 30명의 평가 가능한 환자에서 40%의 객관적 반응률 (ORR)
– 90%의 질병 조절률 (DCR)
– 9.7개월의 중앙 무진행 생존 기간 (PFS)
– 대부분 1/2 등급의 부작용으로 관리가 용이한 안전성 프로필
중대한 2b상 시험은 예정보다 빠르게 환자 모집을 완료했습니다. Cullinan과 Taiho의 파트너십은 2억7500만 달러의 선지급금과 추가 규제 이정표에서 1억3000만 달러의 잠재적 지급을 포함하며, 미국에서 50/50의 수익 배분을 합니다.
Cullinan Therapeutics (CGEM) a présenté des données mises à jour du Module C de l’essai pivot de phase 2b REZILIENT1 pour zipalertinib lors de l’ESMO 2024. L’étude était axée sur des patients atteints de NSCLC portant des mutations d’insertion dans l’exon 20 de l’EGFR qui ont progressé après un traitement par amivantamab. Les principaux résultats incluent :
– 40 % de taux de réponse objective (ORR) chez 30 patients évaluables
– 90 % de taux de contrôle de la maladie (DCR)
– 9,7 mois de survie sans progression médiane (PFS)
– Profil de sécurité gérable avec principalement des événements indésirables de grade 1/2
L’essai pivot de phase 2b a complété le recrutement en avance sur le calendrier. Le partenariat de Cullinan avec Taiho implique un paiement initial de 275 millions de dollars et un potentiel de 130 millions de dollars en jalons réglementaires supplémentaires, avec un partage des bénéfices de 50/50 aux États-Unis.
Cullinan Therapeutics (CGEM) hat auf der ESMO 2024 aktualisierte Daten aus Modul C der entscheidenden Phase 2b REZILIENT1-Studie zu zipalertinib vorgestellt. Die Studie konzentrierte sich auf Patienten mit NSCLC mit Insertionsmutationen im EGFR-Exon 20, die nach einer Behandlung mit Amivantamab progressiert sind. Die wichtigsten Ergebnisse umfassen:
– 40% objektive Ansprechrate (ORR) bei 30 evaluierbaren Patienten
– 90% Krankheitskontrollrate (DCR)
– 9,7 Monate mediane progressionsfreie Überlebenszeit (PFS)
– Handhabbares Sicherheitsprofil mit überwiegend Nebenwirkungen der Grad 1/2
Die entscheidende Phase 2b-Studie schloss die Rekrutierung vorzeitig ab. Cullinans Partnerschaft mit Taiho umfasst eine Vorauszahlung von 275 Millionen Dollar und die Möglichkeit von 130 Millionen Dollar an zusätzlichen regulatorischen Meilensteinen, mit einer 50/50 Gewinnbeteiligung in den USA.
Positive
- 40% objective response rate in patients who progressed after amivantamab treatment
- 90% disease control rate in evaluable patients
- 9.7 months median progression-free survival
- Pivotal Phase 2b trial enrollment completed ahead of schedule
- $275M upfront payment received from Taiho partnership
- Potential for additional $130M in regulatory milestone payments
- 50/50 profit share with Taiho in the U.S. market
Negative
- Majority of patients (60%) did not achieve objective response
- Most common treatment-related adverse events included rash (38%) and paronychia (36%)
The updated data from Cullinan Therapeutics’ zipalertinib trial is highly promising for NSCLC patients with EGFR exon 20 insertion mutations. The 40% objective response rate and 90% disease control rate in heavily pre-treated patients who progressed after amivantamab are impressive. This suggests zipalertinib could become a valuable treatment option in a setting with alternatives.
The manageable safety profile, with mostly grade 1/2 adverse events, is encouraging for long-term tolerability. The 9.7-month progression-free survival indicates potential for durable responses. Importantly, zipalertinib’s selectivity for mutant EGFR may contribute to its efficacy and safety balance.
The accelerated trial enrollment reflects high interest from both clinicians and patients, potentially expediting the drug’s path to market. Overall, these results strengthen zipalertinib’s position as a promising candidate for this difficult-to-treat patient population.
Cullinan Therapeutics’ zipalertinib data presents a strong market opportunity. The consistent 40% response rate in a heavily pre-treated population could position zipalertinib as a go-to therapy for EGFR ex20ins NSCLC patients post-amivantamab, a growing market segment.
The early completion of enrollment for the pivotal Phase 2b study is a positive signal, potentially accelerating the timeline to market. This could give Cullinan a competitive edge in the evolving EGFR ex20ins treatment landscape.
The $275 million upfront payment and potential $130 million in regulatory milestones from Taiho, coupled with a 50% profit share in the U.S., provide Cullinan with strong financial backing and future revenue potential. This partnership structure balances risk and reward, potentially boosting investor confidence in the program’s commercial prospects.
Zipalertinib’s data in post-amivantamab patients addresses a critical unmet need in EGFR ex20ins NSCLC treatment. The consistent efficacy across different patient populations (post-chemotherapy and post-amivantamab) suggests broad applicability. The 3% complete response rate, although small, is noteworthy in this heavily pre-treated population.
The unique chemical structure of zipalertinib, conferring high selectivity for mutant exon 20, may explain its favorable efficacy and safety profile. This could potentially differentiate it from other ex20ins-directed agents.
The ongoing REZILIENT studies, including trials in 1L and 2L+ settings and in patients with brain metastases, demonstrate a comprehensive development strategy. If successful, these could significantly expand zipalertinib’s potential patient population and solidify its position in the EGFR ex20ins NSCLC treatment paradigm.
Updated data show consistent objective response rate of 40% and manageable safety profile in patients with non-small cell lung cancer harboring epidermal growth factor receptor exon 20 insertion mutations treated with zipalertinib who progressed on or after prior amivantamab treatment
Enrollment of pivotal Phase 2b trial complete ahead of schedule
CAMBRIDGE, Mass., Sept. 14, 2024 (GLOBE NEWSWIRE) — Cullinan Therapeutics, Inc. (Nasdaq: CGEM), a biopharmaceutical company focused on developing modality-agnostic targeted therapies, today shared updated data in patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations receiving zipalertinib after prior treatment with amivantamab enrolled in Module C of its pivotal Phase 2b REZILIENT1 clinical trial. Findings from the clinical trial were presented in a Mini Oral session today at the European Society for Medical Oncology Congress 2024 (Presentation Number 1245MO).
As of a March 29, 2024 data cut-off, 45 patients had been enrolled. Patients had received a median of three prior systemic anti-cancer regimens, including prior platinum-based chemotherapy, prior anti-PD1/L1 therapy, and/or prior EGFR tyrosine kinase inhibitor (TKI) therapy, in addition to amivantamab.
At data cut-off, 30 patients were evaluable for response, of which 1 patient (3%) had a complete response (CR), 11 patients (37%) had partial response (PR), and 15 patients (50%) had stable disease (SD), showing similar anti-tumor activity compared with patients receiving zipalertinib after prior chemotherapy in the previously reported Phase 1/2a part of the study.
| | Module C (post chemo and amivantamab+/- other ex20ins treatment) (N=30) |
Phase 1/2a results (post chemo)1 (N=39) |
| ORR (confirmed) | 40% | 41% |
| DCR2 | 90% | 97% |
| DOR (months) | NE | NE |
| PFS (months) | 9.7 | 12 |
NE: Not estimable
ORR: Objective response rate; DCR: Disease control rate; DOR: Duration of response; PFS: Progression-free survival
1 Piotrowska Z, et al. JCO 2023
2 DCR= (CR+PR+SD) / response-evaluable patients
Zipalertinib demonstrated a manageable safety profile, similar to what has been previously reported. The most common treatment-related adverse events in greater than 10% of patients (n=45) were rash (38%), paronychia (36%), anemia (24%), dry skin (20%), dermatitis acneiform (16%), nausea (16%), and stomatitis (11%), the majority of which were grade 1/2. There were no grade 4 or grade 5 treatment-related adverse events.
“We are pleased to share updated data characterizing the potential of zipalertinib for patients with heavily pre-treated EGFR ex20ins mutation NSCLC who progressed on or after amivantamab,” said Jeffrey Jones, MD, MBA, Chief Medical Officer, Cullinan Therapeutics. “With more evaluable patients and longer follow-up, these data continue to strengthen our confidence in the potential of zipalertinib. We remain focused on rapid execution and have successfully completed enrollment of the pivotal Phase 2b study ahead of schedule, which was originally planned for the end of this year. We are pleased to observe consistent positive results throughout the study and continue to advance the program along with our partners at Taiho.”
“This is the first presentation to systematically characterize the anti-tumor activity of zipalertinib, an oral selective tyrosine kinase inhibitor with specific activity against EGFR exon 20 insertion mutations, in heavily treated patients with advanced or metastatic NSCLC harboring EGFR exon 20 insertions-mutation, who have received prior amivantamab,” said Antonio Passaro, MD, PhD, Division of Thoracic Oncology, European Institute of Oncology. “In this setting, which is a significant emerging unmet medical need, zipalertinib demonstrated promising efficacy, including a high overall response rate, and a manageable safety profile.”
Zipalertinib has a unique chemical structure that is distinct from other ex20ins-directed agents, which makes it highly selective for mutant exon 20 versus wild-type EGFR.
Cullinan and Taiho have a broad development program for zipalertinib through a suite of REZILIENT studies, including two ongoing pivotal studies in 1L and 2L+ ex20ins NSCLC as well as studies in other patient populations such as patients with active brain metastases and those with uncommon EGFR mutations.
Cullinan entered into a partnership with Taiho in 2022, receiving an upfront cash payment of $275M and the potential for additional payments totaling $130M to be made for the achievement of U.S. regulatory milestones. Cullinan also retains a 50/50 profit share in the U.S.
About Zipalertinib
Zipalertinib (CLN-081/TAS6417) is an orally available small molecule designed to target activating mutations in EGFR. The molecule was engineered to inhibit EGFR variants with exon 20 insertion mutations, while sparing wild-type EGFR. Zipalertinib is designed as a next generation, irreversible EGFR inhibitor for the treatment of a genetically defined subset of patients with non-small cell lung cancer. Zipalertinib has received Breakthrough Therapy Designation from the U.S. FDA.
Zipalertinib is being developed by Taiho Oncology, Inc., its parent company, Taiho Pharmaceutical Co., Ltd., and Cullinan Therapeutics, Inc. Cullinan Pearl Corp., which Taiho Pharmaceutical Co., Ltd., acquired from Cullinan Therapeutics, Inc. in 2022, previously licensed the rights to zipalertinib in Greater China to Zai Lab Limited in 2020.
About Cullinan Therapeutics
Cullinan Therapeutics, Inc. (Nasdaq: CGEM) is a biopharmaceutical company dedicated to creating new standards of care for patients. Cullinan has strategically built a diversified portfolio of clinical-stage assets that inhibit key drivers of disease or harness the immune system to eliminate diseased cells in both autoimmune diseases and cancer. Cullinan’s portfolio encompasses a wide range of modalities, each with the potential to be best and/or first in class. Anchored in a deep understanding of oncology, immunology, and translational medicine, we create differentiated ideas, identify the most appropriate targets, and select the optimal modality to develop transformative therapeutics across a wide variety of autoimmune and cancer indications. We push conventional boundaries from candidate selection to differentiated therapeutic, applying rigorous go/no go criteria at each stage of development to fast-track only the most promising molecules to the clinic and, ultimately, commercialization. With deep scientific expertise, our teams exercise creativity and urgency to deliver on our promise to bring new therapeutic solutions to patients. Learn more about Cullinan at https://cullinantherapeutics.com/, and follow us on LinkedIn and X.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, express or implied statements regarding Cullinan’s beliefs and expectations regarding the potential benefits and therapeutic potential of zipalertinib; our clinical development plans and timelines; the milestone payments we may receive from Taiho and other statements that are not historical facts. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “hope,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “target,” “should,” “would,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.
Any forward-looking statements in this press release are based on management’s current expectations and beliefs of future events and are subject to known and unknown risks and uncertainties that may cause our actual results, performance or achievements to be materially different from any expressed or implied by the forward-looking statements. These risks include, but are not limited to, the following: uncertainty regarding the timing and results of regulatory submissions; success of our clinical trials and preclinical studies; risks related to our ability to protect and maintain our intellectual property position; risks related to manufacturing, supply, and distribution of our product candidates; the risk that any one or more of our product candidates, including those that are co-developed, will not be successfully developed and commercialized; the risk that the results of preclinical studies or clinical studies will not be predictive of future results in connection with future studies; and success of any collaboration, partnership, license or similar agreements. These and other important risks and uncertainties discussed in our filings with the Securities and Exchange Commission, including under the caption “Risk Factors” in our most recent Annual Report on Form 10-K and subsequent filings with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change, except to the extent required by law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. Moreover, except as required by law, neither the company nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements included in this press release. Any forward-looking statement included in this press release speaks only as of the date on which it was made.
Contact:
Investors
Nick Smith
+1 401.241.3516
nsmith@cullinantx.com
Media
Rose Weldon
+1 215.801.7644
rweldon@cullinantx.com
FAQ
What were the key results from Cullinan Therapeutics’ (CGEM) zipalertinib trial presented at ESMO 2024?
Cullinan Therapeutics reported a 40% objective response rate, 90% disease control rate, and 9.7 months median progression-free survival in NSCLC patients with EGFR exon 20 insertion mutations who progressed after amivantamab treatment.
How does zipalertinib’s safety profile look based on the CGEM trial data?
Zipalertinib demonstrated a manageable safety profile with mostly grade 1/2 adverse events. The most common treatment-related events were rash (38%), paronychia (36%), and anemia (24%), with no grade 4 or 5 events reported.
What is the current status of Cullinan Therapeutics’ (CGEM) pivotal Phase 2b trial for zipalertinib?
Cullinan Therapeutics announced that enrollment for the pivotal Phase 2b trial of zipalertinib has been completed ahead of schedule, originally planned for the end of 2024.
What is the financial arrangement between Cullinan Therapeutics (CGEM) and Taiho for zipalertinib?
Cullinan received a $275M upfront payment from Taiho, with potential for additional $130M in regulatory milestone payments. The companies have a 50/50 profit share agreement for the U.S. market.
